Predictors of Coronary Heart Disease Events Among Asymptomatic Persons With Low Low-Density Lipoprotein Cholesterol: MESA (Multi-Ethnic Study of Atherosclerosis)

Study Questions:

What are the risk factors for coronary artery disease in patients with low low-density lipoprotein cholesterol (LDL-C)?


The authors analyzed the predictors of coronary events among 3,714 participants in the MESA study who were not on any baseline lipid-lowering therapies, and had an LDL-C ≤130 mg/dl. Unadjusted and adjusted hazard ratios were calculated to assess the association of traditional risk factors, biomarkers, and markers of subclinical atherosclerosis (coronary artery calcium [CAC] and carotid intima media thickness [CIMT]) with cardiac events.


There were 120 (3.2%) coronary events over a follow-up of 5.4 years corresponding to an event rate of 5.9% per 1,000 patient-years. Independent predictors of coronary events included age, male sex, hypertension, diabetes, and low HDL-C. CAC but not CIMT was a significant predictor of outcome after adjusting for traditional risk factors. After accounting for all traditional risk factors, the predictive value of CAC was attenuated, but remained highly significant. The relationship of all independent clinical predictors remained robust even after accounting for elevated CAC.


Clinical risk factors and CAC can help predict the risk of subsequent cardiac events in patients with low LDL-C.


This study suggests that traditional risk factors and CAC can be useful in predicting coronary events in patients with low LDL-C. The accuracy of such tools in identifying patients who subsequently proceed to have events is unclear since accurate prediction of extremely low event rates is prone to misclassification. Given declining cost of statins, and rarity of cardiac events, the cost-effectiveness of using imaging to guide selective use of preventive therapy in this population remains unproven.

Clinical Topics: Dyslipidemia, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins

Keywords: Lipoproteins, LDL, Coronary Artery Disease, Follow-Up Studies, Atherosclerosis, Biological Markers, Cholesterol, LDL, Risk Factors

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